FIGURE 12.

Model to describe the roles of ABCA1 in cholesterol homeostasis. A, ABCA1 participates in bidirectional sterol movement at the PM to prevent excess cholesterol accumulation in cells. See text for more detail. B, newly synthesized sterols (lanosterol, cholesterol, etc.) are rapidly transported from the ER to the PM (green line). LDL-Chol exiting the LE moves to the PM or to the ER. In the presence of ABCA1, the ABCA1-regulated, clathrin-independent (ACIE) pathway delivers cholesterol from the PM to the ER (red line) as a major trafficking route, or it releases cholesterol to apoA-I (red line). However, in the absence of ABCA1, such retrograde sterol transport pathway and sterol efflux are reduced or defective, causing cholesterol to be accumulated at the PM and ER sterol sensing to be disrupted. See text for more details. AL, acid lipase; DHL, dihydrolanosterol; EE, early endosome; LAN, lanosterol; LE, late endosome; LY, lysosome; Ub, ubiquitin.